CLINICAL TRIAL SPOTLIGHT

TAPER: Testing a Rescue Strategy

A new clinical trial will test whether triple therapy can help more patients respond to ranibizumab.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

The approval of the anti-vascular endothelial growth factor (VEGF) drug ranibizumab (Lucentis, Genentech) in June 2006 gave new hope to millions of people suffering from age-related macular degeneration (AMD), currently the leading cause of vision loss in the United States. Here was a drug that not only stopped the exudation typical of the "wet" stage of AMD, but it also actually improved vision in clinical trials and therapeutic use. However, thousands of patients who have been treated with ranibizumab have not responded optimally to it.

It is for these patients that the Triple therapy in AMD with PDT to Extend the time to Retreatment (TAPER) trial has been developed. This randomized, masked efficacy study will enroll 100 patients into 2 arms: the first arm will continue patients on ranibizumab monotherapy; the patients in the second arm will receive a triple therapy that includes ranibizumab along with verteporfin (Visudyne, QLT/Novartis), reduced-fluence photodynamic therapy (PDT), and the synthetic glucocorticoid steroidal hormone dexamethasone. The trial is being carried out by Vitreous Retina Macula Consultants of New York in conjunction with QLT Inc. (Vancouver, British Columbia).

Carl Regillo, MD, codirector and a principal investigator with the TAPER study, explained to Retinal Physician the thinking behind the triple therapy to be tested. "This trial is different from other triple-therapy trials," Dr. Regillo says, "because the triple approach is being used as a rescue therapy. This is for patients who have not responded adequately to anti-VEGF treatment alone. They are randomized either into Lucentis monotherapy or the triple therapy arm to get the macula of a patient with active, wet AMD more completely dry or dryer for a longer time frame."

The TAPER study will enroll primary patients who, after 2 to 6 ranibizumab treatments, are still experiencing exudation 4 to 8 weeks following their last treatment.

Dr. Regillo continues, "Other types of patients who may be eligible for the trial are those who need ongoing treatment on a frequent monthly basis who cannot dry up or stay dry with extended treatments. In both arms of the TAPER study, retreatment is based on signs of active disease. This is determined by visual acuity (VA) changes, leakage on fluorescein angiography, and signs of exudation on optical coherence tomography," Dr. Regillo says.

Similar triple-therapy trials have been performed in the past and are currently ongoing, but many of these trials have used triamcinolone acetonide (Kenalog, Bristol-Myers Squibb), rather than dexamethasone. Explaining the choice of dexamethasone over triamcinolone, Dr. Regillo says, "Dexamethasone is similar to triamcinolone but is shorter acting. The shorter action of dexamethasone may be associated with a lower rate of intraocular pressure elevation and a lower rate of cataract progression."

Uncontrolled glaucoma patients will be excluded from the study, as well as patients with subfoveal geographic atrophy or subfoveal fibrosis in the study eye. Furthermore, any patient who has had intraocular surgery in the past 3 months will be deferred.

While this particular combination of drugs has not been tried, Dr. Regillo cites a similar trial recently carried out in Europe. "There has been favorable experience in Europe with a triple-therapy cocktail (reduced-fluence PDT, dexamethasone, and, in Europe, bevacizumab [Avastin, Genentech])," Dr. Regillo says.

The primary endpoint of the TAPER study is mean change in VA from baseline. This would be measured after 12 months of follow-up.

"The secondary endpoints are those that we've become accustomed to in AMD trials, such as percentage of 3-line gain or loss or percentage of patients who gain any letters at all," says Dr. Regillo. "Also, in particular, we will be looking at the total number of treatments. We're hoping that triple therapy has the potential to extend the treatment interval and make for less frequent or less total treatments."

For complete information on the TAPER study, please see the listing on page 61 of this issue. RP